Cutting the Fat: Obesity and Depression

Psychiatric TimesVol 32 No 7
Volume 32
Issue 7

Stress may be a common mediator in both obesity and depression. Here are the top 5 reasons to monitor obesity in depressed patients and practice psychoeducation on a routine basis.

Psychiatrists are faced on a daily basis with depressed patients whose relative inactivity and high BMI are a cause for concern. These patients warrant routine psychoeducation and coordination with primary care physicians who can monitor metabolic indicators, such as lipid profiles. Investment in a good office scale to monitor patient weights is also a good idea.

In his talk on depression and obesity at APA 2015, Julio Licinio, MD, highlighted several important reasons why obesity and depression should be studied:

• The two frequently coexist

• Epidemiological studies suggest that depression can cause obesity and vice versa

• Antidepressants can result in weight gain and are the second most sold drug category in the US

• Stress can cause depression and obesity, and both can have negative cardiometabolic effects

• Depression and obesity are expensive: they cost the US government $210 billion and $147 billion a year, respectively

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The interaction between obesity and depression is bidirectional, and stress may be a common mediator. Chronic stress may result in both disorders. It is well known that glucocorticoids affect numerous body organs and systems, including the liver, muscles, immune system, and cardiovascular system. However, they also affect the CNS.

Repeated stress or chronically elevated glucocorticoid levels can cause atrophy of apical dendrites in CA3 and reduce production of new granule cells in the dentate gyrus causing cognitive impairments.1 This frequently results in cognitive impairments and neuronal loss in limbic regions such as the hippocampus. Stress hormones also affect the immune system. The brain produces its own cytokines that are regulated differently from those in the periphery; this may not imply infection or immune reactivity. These neurokinins contribute to mood, cognition, and behavior.

Leptin has long been recognized as a hormone that signals fullness by binding its receptor in the hypothalamus.2 It has also been suggested that leptin has an important role to play in depression. Animal and human studies have shown that low circulating leptin levels are associated with exposure to chronic stress and with symptoms of depression, such as reduced locomotion and reduced sucrose-seeking in humans.3,4

Findings indicate that antidepressants such as fluoxetine increase neurogenesis via cytokine increase, particularly interleukin (IL)-6 and IL-1α.5 In one study, leptin-deficient mice had reduced brain weight and cortical volume.6 Conversely, other results have shown that neurogenesis in limbic regions was increased in humans and mice treated with leptin.7,8

These findings support the hypothesis that some depressed individuals may lack neurotrophic support because of low levels of circulating leptin, and the presence of chronic stress results in neuronal apoptosis in limbic structures. Replacement of leptin in these individuals may help correct that deficiency. However, financial and regulatory mechanisms have inhibited clinical trials in this area.

Top 5 reasons to monitor obesity in depressed patients

1. The 2 frequently coexist
2. Epidemiological studies suggest that depression can cause obesity and vice versa
3. Antidepressants can result in weight gain and are the second most sold drug category in the US
4. Stress can cause depression and obesity, and both can have negative cardiometabolic effects
5. Depression and obesity are expensive: they cost the US government $210 billion and $147 billion a year, respectively

What is the link to obesity? Since leptin is produced in adipose tissue, shouldn’t overweight individuals have elevated circulating leptin? The answer to the second question is yes. However, animal models and human studies suggest obese individuals may have leptin resistance. This may be caused by defects in the leptin signaling pathway at several levels, including impaired transport of leptin across the blood-brain barrier, reduced function of the leptin receptor, and defects in leptin signal transduction.9 Therefore, depression in obese individuals may also be due to a central deficit in leptin.

I have described how obesity may result in depression in the context of stress. What about the converse-depression resulting in obesity?

In his talk, Dr Licinio attributed this to antidepressant use. He described the rise in subjective stress levels over time experienced by individuals, due to factors such as money, work, economy, and family relationships, as described in the 2012 APA stress survey. This contributes to rising depression. To counteract the rising chronic depression, partly due to stress, Dr Licinio cited the trend of increasing antidepressant use in the US, the UK, and Australia since the late 1990s. Antidepressants have a well-known propensity to cause weight gain, possibly due to peripheral increase in insulin-like growth factor 1 (IGF-1).10 Furthermore, Dr Licinio mentioned that in depressed individuals, exposure to antidepressants for only a short period may have lasting effects on their propensity to gain weight when they are exposed to a high-fat diet. This may be due to epigenetic effects. Thus, the rise in antidepressant use over the past few decades may have contributed to obesity in depressed individuals with chronic stress.

In a world with increasingly scarce resources, it is likely that stress will continue to rise-contributing to depression and obesity. If the past is any indicator, obesity will continue to be an epidemic and may contribute to depression. Conversely, antidepressant use may make weight gain more likely. Neuroendocrine, immunological, and genetic targets such as leptin, IGF-1, and methylated genes may hold promise for future interventions for both of these diseases.

It’s time to cut the fat!

This article was originially posted on June 17, 2015 and has since been updated.


Dr Naidoo is a fourth-year psychiatry resident in the department of psychiatry and behavioral neurosciences at Wayne State University in Detroit.


1. Magariños AM, García Verdugo JM, McEwen BS. Chronic stress alters synaptic terminal structure in hippocampus. Proc Natl Acad Sci U S A. 1997;94: 14002-14008.

2. Elmquist JK, Bjørbaek C, Ahima RS, et al. Distributions of leptin receptor mRNA isoforms in the rat brain. J Comp Neurol. 1998;395:535-547.

3. Katz RJ. Animal model of depression: pharmacological sensitivity of a hedonic deficit. Pharmacol Biochem Behav. 1982;16:965-968.

4. Willner P. Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology. 2005;52:90-110.

5. Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006;59:1116-1127.

6. Ahima RS, Bjørbaek C, Osei S, Flier JS. Regulation of neuronal and glial proteins by leptin: implications for brain development. Endocrinology. 1999;140: 2755-2762.

7. Matochik JA, London ED, Yildiz BO, et al. Effect of leptin replacement on brain structure in genetically leptin-deficient adults. J Clin Endocrinol Metab. 2005;90:2851-2854.

8. Steppan CM, Swick AG. A role for leptin in brain development. Biochem Biophys Res Commun. 1999; 256:600-602.

9. Münzberg H, Myers MG Jr. Molecular and anatomical determinants of central leptin resistance. Nat Neurosci. 2005;8:566-570.

10. Licinio J, Wong ML. The role of inflammatory mediators in the biology of major depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems, and contribute to neurotoxicity and neuroprotection. Mol Psychiatry. 1999;4:317-327.

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